X-linked periventricular heterotopia (also called periventricular nodular heterotopia or PNH) is caused by point mutations or deletions affecting the FLNA gene with presumed loss of function. About 80% of individuals with X-linked periventricular heterotopia have a detectable mutation in the FLNA gene. Most cases of X-linked periventricular heterotopia are caused by point mutations. MLPA analysis of select exons (4, 11, 22, 25, 29, 39, and 46) is also performed.
In addition, FLNA mutations with presumed gain of function are reported in association with four other disorders (Frontometaphyseal dysplasia, Melnick-Needles syndrome, Oto-palato-digital syndrome type I, and Oto-palato-digital syndrome type II). There is overlap of the various findings with these conditions. However, the main features are skeletal findings such as craniofacial abnormalities, scoliosis, and digit abnormalities as well as deafness and genitourinary findings.